THE EFFECT OF MORPHINE ON THE POTASSIUM EVOKED RELEASE OF TRITIATED 5-HYDROXYTRYPTAMINE FROM SPINAL-CORD SLICES IN THE RAT

The effect of morphine on the K (40 mM) evoked release of exogenous [3H]5-HT [5-hydroxytryptamine] from slices of the dorsal spinal cord of the rat was studied. The effects of in vitro applied morphine on the slices were compared to those produced by systemic morphine applied to the animals before preparation of the slices. The in vitro application of morphine (10-6-10-5 M) did not affect the release of [3H]5-HT. It was observed that the K evoked release of [3H]5-HT from the slices of the spinal cord of rats which had received 10 mg/kg s.c. of morphine 30 min beforehand was significantly increased. The effect of systemic morphine was dose-dependent (in the range of 1.5-10 mg/kg s.c.) and could be blocked by prior administration of naloxone (1 mg/kg i.m.) 2 min before the morphine. The acute administration of 10 mg/kg s.c. of morphine, which did not induce analgesia in rats rendered tolerant to morphine, did not modify the [3H]5-HT release. Higher doses of morphine, which have been shown to restore analgesia in these rats, induced an increase in the release which was significant for a dose of 100 mg/kg s.c. These results, demonstrating a specific and dose-dependent increase in the K evoked release of [3H]5-HT from spinal dorsal slices after systemic administration of morphine, emphasize the role of serotonergic systems in such analgesia. The lack of effect of the drug directly applied in vitro favors a supraspinal site of action of the drug and is in agreement with recent results.